Clodazon

Clodazon (AW 142446) is an antidepressant drug investigated in Germany in the 1960s. In animal models, clodazon inhibits the catalepsy induced by tetrabenazine and it potentiates the effect of catecholamines, both effects being of the order experienced with imipramine. In clinical trials, about 2/3 of the patients showed a positive antidepressive effect with few side effects.

Pharmacology:[1][2]

## Synthesis

The synthesis of clodazon is delineated in the patent:[3]

Clodazon synthesis

5-Chloro-2-nitrodiphenylamine [25781-92-4] (1) is reduced to 5-chloro-N-phenylbenzene-1,2-diamine [68406-47-3] (2). Treatment of this with phosgene (caution) would give 3-phenyl-5-chloro-benzimidazolin-2-one [54986-47-9] (3). Base catalyzed treatment of this with 1-bromo-3-chloropropane provided PC20506309 (structure not shown). Displacement of the remaining halogen atom leaving group by dimethylamine completes the construction of sidechain and thus the synthesis of clodazon (4).

[54986-47-9] ~98%:[4]~90%:[5]

The crystal structure is monoclinic with space group P21/c with unit cell parameters a=5.898 b=31.911 c=10.817 Å with β=103.52°. Unit cell volume is 1989.3 Å3.[6]

## References

1. ↑ "Ein Antidepressivum aus der Gruppe der 2-Benzimidazolinone.". International Pharmacopsychiatry 1 (3-4): 214–210. August 1968. doi:10.1159/000467934.
2. ↑ "[Clinical experiences with the antidepressive agent AW 14'2446 (Clodazon)]". Wiener Medizinische Wochenschrift 119 (7): 130–133. February 1969. PMID 5772001.
3. ↑ BE659364 (1965) idem Hunziker Fritz, US3338916 (1967 to A Wander S A Dr).
4. ↑ "Compounds With Antiulcer and Antisecretory Activity. I: 3-Aryl-benzimidazolin-2-ones and -thiones". European Journal of Medicinal Chemistry 16 (4): 321–326. 1981.
5. ↑ "Role of alkali halides in the synthesis of nitrogen containing heterocycles by reductive carbonylation of aromatic nitro-derivatives catalysed by Ru3(CO)12". Journal of the Chemical Society, Perkin Transactions 2 (4): 913. 1994. doi:10.1039/p29940000913.
6. ↑ "5-Chloro-1-[3-(dimethylamino)propyl]-1,3-dihydro-3-phenyl-2 H -benzimidazol-2-one monohydrochloride monohydrate (clodazone)". Acta Crystallographica Section B Structural Crystallography and Crystal Chemistry 34 (8): 2656–2658. 1 August 1978. doi:10.1107/S0567740878008894. Bibcode: 1978AcCrB..34.2656L.

* v
* t
* e

Antidepressants (N06A)

Specific reuptake inhibitors and/or receptor modulators

| SSRIs|

* Citalopram
* Escitalopram
* Fluoxetine#
* Fluvoxamine
* Indalpine‡
* Paroxetine
* Sertraline
* Zimelidine‡

|

SNRIs|

* Desvenlafaxine
* Duloxetine
* Levomilnacipran
* Milnacipran
* Tofenacin
* Venlafaxine

NRIs|

* Atomoxetine
* Reboxetine
* Viloxazine

NDRIs|

* Amineptine‡
* Bupropion
* Nomifensine‡

NaSSAs|

* Mianserin
* Mirtazapine
* Setiptiline

SARIs|

* Etoperidone
* Nefazodone
* Trazodone

SMS|

* Vilazodone
* Vortioxetine

Others|

* Agomelatine
* Amisulpride
* Esketamine†
* Etryptamine‡
* Indeloxazine
* flupentixol
* Ketamine†
* Medifoxamine‡
* Metryptamine‡
* Oxaflozane‡
* Pivagabine‡
* Tandospirone
* Teniloxazine
* Tianeptine

Tricyclic and tetracyclic antidepressants

| TCAs|

* Amineptine‡
* Amitriptyline#
* Amitriptylinoxide
* Butriptyline‡
* Clomipramine#
* Demexiptiline‡
* Desipramine
* Dibenzepin
* Dimetacrine‡
* Dosulepin
* Doxepin
* Imipramine
* Imipraminoxide‡
* Iprindole‡
* Lofepramine
* Melitracen
* Metapramine‡
* Nitroxazepine
* Nortriptyline
* Noxiptiline
* Opipramol
* Pipofezine
* Propizepine‡
* Protriptyline
* Quinupramine‡
* Tianeptine
* Trimipramine

|

TeCAs|

* Amoxapine
* Maprotiline
* Mianserin
* Mirtazapine
* Setiptiline

Others|

* Tiazesim

Monoamine oxidase inhibitors

| Non-selective|

* Irreversible: Benmoxin‡
* Iproclozide‡
* Iproniazid‡
* Isocarboxazid
* Isoniazid#
* Linezolid#
* Mebanazine‡
* Nialamide‡
* Octamoxin‡
* Phenelzine
* Pheniprazine‡
* Phenoxypropazine‡
* Pivhydrazine‡
* Safrazine‡
* Tedizolid
* Tranylcypromine

* Reversible: Caroxazone‡

* Mixed: Bifemelane

|

MAOA-selective|

* Reversible: Eprobemide
* Metralindole
* Minaprine‡
* Moclobemide
* Pirlindole
* Tetrindole
* Toloxatone

MAOB-selective|

* Irreversible: Selegiline

Adjunctive therapies

* Atypical antipsychotics (aripiprazole, brexpiprazole, lurasidone, olanzapine, quetiapine, risperidone)
* Buspirone
* Lithium (lithium carbonate, lithium citrate)
* Thyroid hormones (triiodothyronine (T3), levothyroxine (T4))

Miscellaneous

* Ademetionine (SAMe)
* Hypericum perforatum (St. John's Wort)
* Oxitriptan (5-HTP)
* Rubidium chloride (RbCl)
* Tryptophan

* #WHO-EM
* ‡Withdrawn from market
* Clinical trials:
* †Phase III
* §Never to phase III

* v
* t
* e

Monoamine reuptake inhibitors

DAT
(DRIs)|

* Piperazines: DBL-583
* GBR-12783
* GBR-12935
* GBR-13069
* GBR-13098
* Nefazodone
* Vanoxerine

* Piperidines: 4-Fluoropethidine
* Benocyclidine (BTCP)
* Desoxypipradrol
* Dexmethylphenidate
* Difemetorex
* Ethylphenidate
* HDMP-28
* Methylphenidate
* Pethidine (meperidine)
* Phencyclidine
* Pipradrol
* Tenocyclidine

* Pyrrolidines: Diphenylprolinol
* MDPV
* Naphyrone
* Prolintane
* Pyrovalerone

* Tropanes: Altropane
* Benzatropine (benztropine)
* Brasofensine
* CFT
* Cocaine
* Dichloropane
* Difluoropine
* Etybenzatropine (ethybenztropine)
* FE-β-CPPIT
* FP-β-CPPIT
* Ioflupane (123I)
* RTI-55
* RTI-112
* RTI-113
* RTI-121
* RTI-126
* RTI-150
* RTI-177
* RTI-229
* RTI-336
* Tesofensine
* Troparil
* Tropoxane
* WF-11
* WF-23
* WF-31
* WF-33

* Others: Adrafinil
* Amifitadine
* Armodafinil
* Amfonelic acid
* Amineptine
* Ansofaxine
* BTQ
* BTS 74,398
* Bupropion
* Chaenomeles speciosa
* Ciclazindol
* Dasotraline
* Desmethylsertraline
* Desmethylsibutramine
* Diclofensine
* Didesmethylsibutramine
* Dimethocaine
* Diphenylpyraline
* Dizocilpine (MK-801)
* DOV-102,677
* DOV-216,303
* Efavirenz
* Ephenidine
* Esketamine
* EXP-561
* Fencamfamin
* Fezolamine
* Fluorenol
* GYKI-52895
* Indatraline
* Ketamine
* Lefetamine
* Levophacetoperane
* Liafensine
* LR-5182
* Manifaxine
* Mazindol
* Medifoxamine
* Mesocarb
* Metaphit
* MIN-117 (WF-516)
* Modafinil
* Nefopam
* Nomifensine
* NS-2359
* O-2172
* Oroxylin A
* Perafensine
* Pridefine
* Radafaxine
* Rimcazole
* Sertraline
* Sibutramine
* Solriamfetol
* Tametraline
* Tedatioxetine
* Tripelennamine
* Venlafaxine

NET
(NRIs)|

* Selective norepinephrine reuptake inhibitors: Amedalin
* Alseroxylon
* Ciclazindol
* Daledalin
* Edivoxetine
* Esreboxetine
* Lortalamine
* Mazindol
* Nisoxetine
* Reboxetine
* Talopram
* Talsupram
* Tandamine
* Teniloxazine
* Viloxazine

* Norepinephrine–dopamine reuptake inhibitors: Amineptine
* Bupropion
* Fencamine
* Fencamfamin
* Hydroxybupropion
* Lefetamine
* Levophacetoperane
* LR-5182
* Manifaxine
* Methylphenidate
* Nomifensine
* O-2172
* Radafaxine
* Solriamfetol

* Serotonin–norepinephrine reuptake inhibitors: Atomoxetine (tomoxetine)
* BTS-54505
* CP-39,332
* Desvenlafaxine
* Duloxetine
* Eclanamine
* Levomilnacipran
* McN-5652
* Milnacipran
* N-Methyl-PPPA
* Nafenodone
* PPPA
* Tofenacin
* Venlafaxine
* WY-45233

* Serotonin–norepinephrine–dopamine reuptake inhibitors: 3,3-Diphenylcyclobutanamine
* Amifitadine
* Ansofaxine
* Bicifadine
* Brasofensine
* Centanafadine
* Cocaine
* Dasotraline
* Desmethylsertraline
* Desmethylsibutramine
* Diclofensine
* Didesmethylsibutramine
* DOV-102677
* DOV-216303
* EXP-561
* Fezolamine
* HDMP-28
* Indatraline
* JNJ-7925476
* JZ-IV-10
* Liafensine
* Mazindol
* Naphyrone
* Nefazodone
* Nefopam
* NS-2359
* Perafensine
* PRC200
* Pridefine
* SEP-228431
* SEP-228432
* Sibutramine
* Tedatioxetine
* Tesofensine
* Tropanes (e.g., cocaine)

* Tricyclic antidepressants: Amitriptyline
* Butriptyline
* Cianopramine
* Clomipramine
* Desipramine
* Dosulepin (dothiepin)
* Doxepin
* Imipramine
* Lofepramine
* Melitracen
* Nortriptyline
* Protriptyline
* Trimipramine

* Tetracyclic antidepressants: Amoxapine
* Maprotiline
* Mianserin
* Oxaprotiline
* Setiptiline

* Others: Antihistamines (e.g., brompheniramine, chlorphenamine, pheniramine, tripelennamine)
* Antipsychotics (e.g., loxapine, ziprasidone)
* Arylcyclohexylamines (e.g., ketamine, phencyclidine)
* Dopexamine
* Ephenidine
* Ginkgo biloba
* Indeloxazine
* Nefazodone
* Opioids (e.g., Desmetramadol|Desmetramadol]]]], methadone, pethidine (meperidine), tapentadol, tramadol, Levorphanol

SERT
(SRIs)|

* Selective serotonin reuptake inhibitors: Alaproclate
* Centpropazine
* Cericlamine
* Citalopram
* Dapoxetine
* Desmethylcitalopram
* Didesmethylcitalopram
* Escitalopram
* Femoxetine
* Fluoxetine
* Fluvoxamine
* Indalpine
* Ifoxetine
* Norfluoxetine
* Omiloxetine
* Panuramine
* Paroxetine
* PIM-35
* Pirandamine
* RTI-353
* Seproxetine
* Sertraline
* Zimelidine

* Selective serotonin reuptake inhibitors and serotonin receptor modulators: Etoperidone
* Litoxetine
* Lubazodone
* LY-393558
* SB-649915
* TGBA01AD
* Trazodone
* Vilazodone
* Vortioxetine

* Serotonin–norepinephrine reuptake inhibitors: Atomoxetine (tomoxetine)
* Bicifadine
* BTS-54505
* CP-39332
* Desvenlafaxine
* Duloxetine
* Eclanamine
* Levomilnacipran
* McN-5652
* Milnacipran
* N-Methyl-PPPA
* PPPA
* Tofenacin
* Venlafaxine
* WY-45233

* Serotonin–norepinephrine–dopamine reuptake inhibitors: 3,3-Diphenylcyclobutanamine
* Amifitadine
* Ansofaxine
* Bicifadine
* Brasofensine
* Centanafadine
* Cocaine
* Dasotraline
* Desmethylsertraline
* Desmethylsibutramine
* Diclofensine
* Didesmethylsibutramine
* DOV-102677
* DOV-216303
* EXP-561
* Fezolamine
* HDMP-28
* Indatraline
* JNJ-7925476
* JZ-IV-10
* Liafensine
* Mazindol
* Naphyrone
* Nefazodone
* Nefopam
* NS-2359
* Perafensine
* PRC200
* Pridefine
* SEP-228431
* SEP-228432
* Sibutramine
* Tedatioxetine
* Tesofensine
* Tropanes (e.g., cocaine)

* Tricyclic antidepressants: Amitriptyline
* Cianopramine
* Clomipramine
* Cyanodothiepin
* Desipramine
* Dosulepin (dothiepin)
* Doxepin
* Imipramine
* Lofepramine
* Nortriptyline
* Pipofezine
* Protriptyline

* Others: A-80426
* Amoxapine
* Antihistamines (e.g., brompheniramine, [[Chemistry:Chlorphenchlorphenamine]], dimenhydrinate, diphenhydramine, mepyramine (pyrilamine), pheniramine, Chemistry:Tripelennamine

VMATs|

* Amiodarone
* Amphetamines (e.g., amphetamine, methamphetamine, MDMA)
* APP
* AZIK
* Bietaserpine
* Deserpidine
* Deutetrabenazine
* Dihydrotetrabenazine
* Efavirenz
* GBR-12935
* GZ-793A
* Ibogaine
* Ketanserin
* Lobeline
* Methoxytetrabenazine
* Reserpine
* Rose bengal
* Tetrabenazine
* Valbenazine
* Vanoxerine (GBR-12909)

Others|

* DAT enhancers: Luteolin

* DAT modulators: Agonist-like: SoRI-9804
* SoRI-20040; Antagonist-like: SoRI-20041

See also: Receptor/signaling modulators • Monoamine releasing agents • Adrenergics • Dopaminergics • Serotonergics • Monoamine metabolism modulators • Monoamine neurotoxins

* v
* t
* e

Tricyclics

Classes|

* Acridine
* Anthracene
* Dibenzazepine
* Dibenzocycloheptene
* Dibenzodiazepine
* Dibenzothiazepine
* Dibenzothiepin
* Dibenzoxazepine
* Dibenzoxepin
* Phenothiazine
* Pyridazinobenzoxazine
* Pyridinobenzodiazepine
* Thioxanthene

Antidepressants
(TCAs and TeCAs)|

* 7-OH-Amoxapine
* Amezepine
* Amineptine
* Amitriptyline
* Amitriptylinoxide
* Amoxapine
* Aptazapine
* Azepindole
* Azipramine
* Batelapine
* Butriptyline
* Cianopramine
* Ciclazindol
* Ciclopramine
* Cidoxepin
* Clomipramine
* Cotriptyline
* Cyanodothiepin
* Demexiptiline
* Depramine (balipramine)
* Desipramine (desmethylimipramine)
* Desmethylclomipramine
* Desmethyltrimipramine
* Dibenzepin
* Dimetacrine
* Dosulepin (dothiepin)
* Doxepin
* Enprazepine
* Esmirtazapine
* Fantridone
* Fluotracen
* Hepzidine
* Homopipramol
* Imipramine
* Imipraminoxide
* Intriptyline
* Iprindole
* Ketipramine
* Litracen
* Lofepramine
* Losindole
* Loxapine
* Maprotiline
* Mariptiline
* Mazindol
* Melitracen
* Metapramine
* Mezepine
* Mianserin
* Mirtazapine
* Monometacrine
* Naranol
* Nitroxazepine
* Norbutriptyline
* Nordoxepin
* Northiaden (nordosulepin)
* Nortriptyline (noramitriptyline)
* Noxiptiline
* Octriptyline
* Opipramol
* Oxaprotiline
* Pipofezine
* Pirandamine
* Propizepine
* Protriptyline
* Quinupramine
* Setiptiline (teciptiline)
* Spiroxepin
* Tandamine
* Tampramine
* Tianeptine
* Tienopramine
* Trimipramine

Antihistamines|

* Azatadine
* Bisulepin
* Clobenzepam
* Cyproheptadine
* Dacemazine
* Deptropine
* Desloratadine
* Epinastine
* Etymemazine
* Fenethazine
* Hydroxyethylpromethazine
* Isopromethazine
* Isothipendyl
* Ketotifen
* Latrepirdine
* Loratadine
* Mebhydrolin
* Mequitazine
* Methdilazine
* Olopatadine
* Oxomemazine
* Phenindamine
* Pimethixene
* Promethazine
* Propiomazine
* Rupatadine
* Thiazinamium

Antipsychotics|

* Acetophenazine
* Alimemazine
* Amoxapine
* Asenapine
* Butaclamol
* Butaperazine
* Carfenazine (carphenazine)
* Carpipramine
* Chlorpromazine
* Chlorprothixene
* Ciclindole
* Citatepine
* Clocapramine
* Clomacran
* Clorotepine
* Clotiapine
* Clozapine
* Cyanothepin
* Doclothepin
* Docloxythepin
* Erizepine
* Flucindole
* Flumezapine
* Fluotracen
* Flupentixol
* Fluphenazine
* Gevotroline
* Homopipramol
* Isofloxythepin
* Levomepromazine/Methotrimeprazine
* Loxapine
* Lurasidone
* Maroxepin
* Meperathiepin
* Mesoridazine
* Metiapine
* Metitepine
* Metoxepin
* Mosapramine
* Naranol
* Octomethothepin
* Olanzapine
* Oxyclothepin
* Oxyprothepin
* Pentiapine
* Peradithiepin
* Perathiepin
* Perazine
* Perphenazine
* Periciazine
* Pinoxepin
* Piperacetazine
* Pipotiazine
* Piquindone
* Prochlorperazine
* Promazine
* Prothipendyl
* Quetiapine
* Savoxepin/Cipazoxapine
* Sulforidazine
* Tenilapine
* Thiethylperazine
* Thiopropazate
* Thioridazine
* Thiothixene
* Tilozepine
* Traboxopine
* Trifluoperazine
* Triflupromazine
* Trifluthepin
* Zotepine
* Zuclopenthixol

Anticonvulsants|

* Carbamazepine
* Dizocilpine
* Eslicarbazepine
* Eslicarbazepine acetate
* Etazepine
* Licarbazepine
* Oxcarbazepine
* Oxitriptyline
* Rispenzepine

Others|

* Adosopine
* Aminopromazine
* Atiprosin
* Beloxepin
* Benzoctamine
* Carvedilol
* Cidoxepin
* Cyclobenzaprine
* Damotepine
* Darenzepine
* Elanzepine
* Fluradoline
* Methylene blue
* Monatepil
* Nuvenzepine
* Oxetorone
* Perlapine
* P7C3
* Pinadoline
* Pirenzepine
* Pirolate
* Pitrazepin
* Pizotifen
* Profenamine
* Serazapine
* Siltenzepine
* Telenzepine
* Tipindole
* Tropatepine
* Zolenzepine

0.00

(0 votes)

Original source: https://en.wikipedia.org/wiki/Clodazon. Read more

|

Retrieved from "https://handwiki.org/wiki/index.php?title=Chemistry:Clodazon&oldid=4036587"
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[NRIs]: Norepinephrine reuptake inhibitors
*[NDRIs]: Norepinephrine–dopamine reuptake inhibitors
*[NaSSAs]: Noradrenergic and specific serotonergic antidepressants
*[SARIs]: Serotonin antagonist and reuptake inhibitors
*[SMS]: Serotonin modulator and stimulators
*[TCAs]: Tricyclic antidepressants
*[TeCAs]: Tetracyclic antidepressants
*[MAOA]: Monoamine oxidase A
*[MAOB]: Monoamine oxidase B
*[SAMe]: S-adenosyl-L-methionine
*[5-HTP]: 5-hydroxytryptophan
*[DAT]: Dopamine transporter
*[DRIs]: Dopamine reuptake inhibitors
*[NET]: Norepinephrine transporter
*[SERT]: Serotonin transporter
*[SRIs]: Serotonin reuptake inhibitors
*[VMATs]: Vesicular monoamine transporters